Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153
+
PD-1
+
CD4
+
senescence-associated T (SAT) cells and CD30
+
T-bet
+
age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis, and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153/CD30 signaling in TLT formation and propose targeting the CD153/CD30 signaling pathway as a therapeutic target for slowing kidney disease progression.
To clarify the impact of comorbidities on treatment strategies and outcomes in patients with rheumatoid arthritis (RA) using a large observational RA cohort, the presence of comorbidities was assessed using the Charlson Comorbidity Index (CCI). Changes in medication, disease activity by Disease Activity Score-28 joint count (DAS28) over 6 months, disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), and quality of life by EuroQOL-5-Dimensions (EQ-5D) over 1 year in patients with high disease activity (DAS28 > 5.1) at baseline were assessed according to age-adjusted CCI (CCI(A)) and categorized into four groups (CCI(A) 0, 1-2, 3-4, and ≥5). Among 5,317 patients, 975 patients (18.3%) had at least one comorbidity listed by CCI. DAS28, J-HAQ, and EQ-5D increased in severity with increased CCI(A) levels. Among patients with high disease activity (n = 267), treatment with methotrexate and/or biologics and improved DAS28 scores, shown by attenuated intensity, were associated with increased CCI(A) levels. J-HAQ improved from 1.29 ± 0.31 to 0.87 ± 0.37 in 1 year in the CCI(A) 0 group. The adjusted difference (standard error) in J-HAQ at 1 year in CCI(A) 1-2, 3-4, and ≥5 groups was worse than J-HAQ in the CCI(A) 0 group by 0.32 (0.09, p < 0.001), 0.45 (0.10, p < 0.001), and 0.45 (0.15, p < 0.01), respectively. The magnitude of improvement of EQ-5D was significantly attenuated with increasing CCI(A) levels. Thus, patients with comorbidities may not experience the same degree of benefit from recent RA treatments compared with patients without comorbidities in daily practice.
Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34-positive (CD34 + ) cells, in maintenance of cerebral blood flow. In this study, we investigated the link between the level of circulating CD34 + cells and neovascularization at ischemic brain. Compared with control subjects, a remarkable increase of circulating CD34 + cells was observed in patients with angiographic moyamoya vessels, although no significant change was observed in patients with major cerebral artery occlusion (or severe stenosis) but without moyamoya vessels. Our results suggest that the increased level of CD34 + cells associated with ischemic stress is correlated with neovascularization at human ischemic brain.
Conservation priorities and decisions can be informed by understanding diversity patterns and the evolutionary history of ecosystems, and phylogenetic metrics can contribute to this. This project used a range of diversity metrics in concert to examine diversity patterns in the Sunshine Coast heathlands, an ecosystem under intense pressure. The species richness and composition of 80 heathland sites over nine regional ecosystems of heathland on the Sunshine Coast were enhanced with phylogenetic metrics, determined by barcoding 366 heath species of the region. The resulting data were added to an existing phylogeny of regional rainforest species. The diversity metrics for sites and regional ecosystems were compared using univariate and multivariate statistics. The phylogeny from this study, and the low phylogenetic diversity of the heathlands, is consistent with the theory that heath species evolved on the fringes on a wider Australian rainforest flora. Distinctive heathland communities were highlighted, and the existence of geographically scattered, but compositionally similar, phylogenetically even sites points to a possible “refugial environment”, characterised by moisture and instability. This suggests contrasting conservation implications: the protection of distinctive communities but also the management of the dynamic processes in other wet and alluvial “refugial environments”. The potential for more focused conservation priorities is enhanced.
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